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Amyotrophic Lateral Sclerosis &... Feb 2024Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with upper and lower motor neuron degeneration and necrosis, characterized by... (Review)
Review
OBJECTIVE
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with upper and lower motor neuron degeneration and necrosis, characterized by progressive muscle weakness, atrophy, and paralysis. The mutation-associated ALS has been classified as ALS6. We reported a case of ALS6 with de novo mutation and investigated retrospectively the characteristics of cases with mutation.
METHODS
We reported a male patient with a new heterozygous variant of the gene and comprehensively reviewed 173 ALS cases with mutation. The literature was reviewed from the PubMed MEDLINE electronic database (https://www.ncbi.nlm.nih.gov/pubmed) using "Amyotrophic Lateral Sclerosis and mutation" or " mutation" as key words from 1 January 2009 to 1 January 2022.
RESULTS
We report a case of ALS6 with a new mutation point (c.1225-1227delGGA) and comprehensively review 173 ALS cases with mutation. Though ALS6 is all with mutation, it is still a highly heterogenous subtype. The average onset age of ALS6 is 35.2 ± 1.3 years, which is much lower than the average onset age of ALS (60 years old). Juvenile FUS mutations have an aggressive progression of disease, with an average time from onset to death or tracheostomy of 18.2 ± 0.5 months. gene has the characteristics of early onset, faster progress, and shorter survival, especially in deletion mutation p.G504Wfs *12 and missense mutation of p.P525L.
CONCLUSIONS
ALS6 is a highly heterogenous subtype. Our study could allow clinicians to better understand the non-ALS typical symptoms, phenotypes, and pathophysiology of ALS6.
Topics: Humans; Male; Amyotrophic Lateral Sclerosis; Mutation; Mutation, Missense; Neurodegenerative Diseases; Retrospective Studies; RNA-Binding Protein FUS
PubMed: 37926865
DOI: 10.1080/21678421.2023.2272170 -
Scientific Reports Oct 2023Molecular biomarkers have the potential to predict the recurrence risk of early-stage lung adenocarcinoma (LUAD) after complete resection, but the study results are... (Meta-Analysis)
Meta-Analysis
Molecular biomarkers have the potential to predict the recurrence risk of early-stage lung adenocarcinoma (LUAD) after complete resection, but the study results are controversial. We aimed to clarify the association of molecular alterations with disease-free survival (DFS) and recurrence-free survival (RFS) in early-stage LUAD with R0 resection. Comprehensive searches were conducted in PubMed/MEDLINE, Web of Science, and Cochrane Library for this systematic review and meta-analysis with date restrictions from 2012 to 2022. In the 18 included studies, data from a total of 7417 participants in 11 studies and 4167 participants in 9 studies were collected for the EGFR and KRAS meta-analyses, respectively. Two studies were assessed as having a moderate risk of bias, and the others were all assessed as having a high individual risk of bias. The molecular alterations in KRAS rather than EGFR, were associated with a high risk of recurrence for early-stage LUAD patients suffering from R0 resection, especially for those in pStage I, the pooled hazard ratios (HRs) of KRAS were 2.71 (95% CI, 1.81-4.06; I = 22%; P < 0.00001) and 1.95 (95% CI, 1.25-3.20; I = 57%; P = 0.003) with small interstudy heterogeneity in univariate and multivariate analyses, respectively. This finding suggests that molecular alterations in KRAS that could be detected by polymerase chain reaction techniques would provide new insight into stratifying risk and personalizing patient postoperative follow-up.
Topics: Humans; Proto-Oncogene Proteins p21(ras); Adenocarcinoma of Lung; Prognosis; Lung Neoplasms; ErbB Receptors
PubMed: 37907475
DOI: 10.1038/s41598-023-42851-2 -
Biomedical Papers of the Medical... Dec 2023HPV16 status in oropharyngeal cancer (OPC) is an important prognostic factor. Its determination, based on immunistochemical analysis of p16 oncoprotein requires an... (Review)
Review
HPV16 status in oropharyngeal cancer (OPC) is an important prognostic factor. Its determination, based on immunistochemical analysis of p16 oncoprotein requires an invasive biopsy. Thus, alternative methods are being sought. Determining oral HPV16 status appears to be a promising alternative. However, it is not used routinely. This prompted us to perform a systematic literature review enabling us to evaluate the diagnostic and predictive ability of this approach. Thirty-four relevant studies were finally selected. For determination of HPV status in OPC, the calculated average sensitivity and specificity for oral sampling was 74% and 91%, respectively, with p16 tumour tissue marker being the gold standard. The method appears to be valuable in monitoring treatment response as well as the biological activity of the tumour, enabling early detection of persistent or relapsing carcinoma sufficiently long before its clinical and/or radiological manifestation. It can also contribute to identification of the primary tumour in cases of metastases of unknown origin. Last but not least, the screening HPV oral testing would help to identify individuals with persistent HPV oral infection who are at increased risk of development of OPC.
Topics: Humans; Papillomavirus Infections; Neoplasm Recurrence, Local; Oropharyngeal Neoplasms; Carcinoma; Sensitivity and Specificity; Biomarkers, Tumor
PubMed: 37901925
DOI: 10.5507/bp.2023.040 -
Cureus Sep 2023The information for protein synthesis is given by the genes. These proteins are responsible for controlling functions like cell growth, differentiation, cell... (Review)
Review
The information for protein synthesis is given by the genes. These proteins are responsible for controlling functions like cell growth, differentiation, cell maturation, and cell death. In the case of genetic mutations, the protein functions get disturbed leading to a drastic shift in the normal physiological functions of cell growth, differentiation, and proliferation, making the normal cell cancerous. The Harvey rat sarcoma virus (HRAS) gene is an oncogene that belongs to the rat sarcoma virus (RAS) family. HRAS gene provides the instructions for making the HRAS protein that plays an important role in regulating cell division and when the HRAS gene gets mutated it gets involved in initiating cancer. HRAS mutation has been frequently noted in head and neck cancers; however, the mechanism of HRAS mutation involved in the initiation of oral squamous cell carcinoma (OSCC) still remains unexplored. An elaborate systematic literature search was done in PubMed, Scopus, and Web of Science databases. It was found that the Ras-dependent mutations affect the involved upstream and downstream components of the Ras-Raf-MAPK (rat sarcoma virus-rapidly accelerated fibrosarcoma-mitogen-activated protein kinase) pathway deregulating the signal leading to tumorigenesis. The Ras mutation can affect the Ras-Raf-MAPK pathway at different stages. The disease caused is based on the frequency of the HRAS mutation and it can lead to diverse cellular outcomes as it is mainly associated with cell division, differentiation, growth, survival, and the cell cycle. The crosstalk between the signaling pathways is controlled by the signaling molecules resulting in the creation of molecular networks. The balance of these molecular networks is very important to determine the cellular outcome. This systematic review inspects the molecular network of HRAS and its vital role in carcinogenesis. It is aimed at exploring and summarizing the contributions of the HRAS mutation involved in the pathogenesis of OSCC.
PubMed: 37868370
DOI: 10.7759/cureus.45505 -
BMC Cancer Oct 2023N-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
N-myc downstream-regulated gene-1 (NDRG1) is well-described as a potent metastasis suppressor, but its role in human breast cancer remains controversial and unclear. Therefore, the present study utilized a systematic review and meta-analysis approach to synthesize the association between NDRG1 protein expression and the aggressive characteristics of breast cancer.
METHODS
The protocol for the systematic review and meta-analysis was registered on the PROSPERO website (CRD42023414814). Relevant articles were searched for in PubMed, Scopus, Embase, MEDLINE, and Ovid between March 30, 2023, and May 5, 2023. The included studies were critically evaluated using the Joanna Briggs Institute critical appraisal tools. The results from individual studies were qualitatively synthesized using textual narrative synthesis. Using a random-effects model, the pooled log odds ratio of effect estimate was used to look at the link between NDRG1 protein expression and aggressive features of breast cancer, such as tumor grade, tumor stage, metastasis to the axillary lymph nodes, and hormonal receptor status.
RESULTS
A total of 1423 articles were retrieved from the electronic database search, and six studies that met the eligibility criteria were included for synthesis. There was an association between the expression of NDRG1 protein and the status of the axillary lymph nodes (P = 0.01, log Odds Ratio (OR): 0.59, 95% Confidence Interval (CI): 0.13-1.05, I: 24.24%, 292 breast cancer cases with positive axillary lymph nodes and 229 breast cancer cases with negative axillary lymph nodes, 4 studies). NDRG1 protein expression and human epidermal growth factor receptor 2 (Her2) status were found to have a negative relationship (P = 0.01, log OR: -0.76, 95% CI: -1.32-(-0.20), I: 32.42%, 197 breast cancer cases with Her2 positive and 272 breast cancer cases with Her2 negative, 3 studies). No correlation was found between NDRG1 protein expression and tumor grade (P = 0.10), estrogen receptor (ER) status (P = 0.57), or progesterone receptor (PR) status (P = 0.41).
CONCLUSION
The study concluded that increased NDRG1 protein expression was associated with increased metastasis of the tumor to the axillary lymph node. Additionally, increased NDRG1 protein expression was observed in Her2-negative breast cancer, suggesting its role in both less aggressive and more aggressive behavior depending on breast cancer subtypes. Based on the findings of the meta-analysis, an increase in NDRG1 protein expression was associated with aggressive characteristics of breast cancer.
Topics: Female; Humans; Axilla; Breast Neoplasms; Cell Cycle Proteins; Intracellular Signaling Peptides and Proteins; Lymph Nodes; Receptor, ErbB-2; Receptors, Progesterone
PubMed: 37858101
DOI: 10.1186/s12885-023-11517-7 -
JNCI Cancer Spectrum Jan 2024Colorectal cancer (CRC) is the second most common cause of cancer death globally. Recent clinical trials suggest an emerging role for HER2 as a potential clinically... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Colorectal cancer (CRC) is the second most common cause of cancer death globally. Recent clinical trials suggest an emerging role for HER2 as a potential clinically relevant biomarker in CRC. Testing for HER2 in CRC is not standard practice; consequently, the prevalence of HER2 positivity (HER2+) in patients with CRC remains uncertain.
METHODS
A systematic literature review and meta-analysis were conducted to generate estimates of proportions of patients with CRC with HER2 overexpression or HER2 amplification and HER2+ (either overexpression or amplification), overall and in patients with rat sarcoma virus (RAS) wild-type cancer. HER2+ was defined as 1) immunohistochemistry with a score of 3+, 2) immunohistochemistry with a score of 2+ and in situ hybridization+, or 3) next-generation sequencing positive.
RESULTS
Of 224 studies identified with information on HER2 in CRC, 52 studies used a US Food and Drug Administration-approved assay and were selected for further analysis. Estimated HER2+ rate was 4.1% (95% confidence interval [CI] = 3.4% to 5.0%) overall (n = 17 589). HER2+ rates were statistically higher in RAS wild-type (6.1%, 95% CI = 5.4% to 6.9%) vs RAS mutant CRC (1.1%, 95% CI = 0.3% to 4.4%; P < .0001). Despite limited clinical information, we confirmed enrichment of HER2+ CRC in patients with microsatellite stable and left-sided CRC.
CONCLUSION
This meta-analysis provides an estimate of HER2+ CRC and confirms enrichment of HER2 in microsatellite stable, left-sided, RAS wild-type CRC tumors. Our work is important given the recently described clinical efficacy of HER2-targeted therapies in HER2+ CRC and informs strategies for incorporation of HER2 testing into standard of care.
Topics: United States; Humans; Receptor, ErbB-2; Biomarkers, Tumor; Treatment Outcome; Immunohistochemistry; Colorectal Neoplasms
PubMed: 37815820
DOI: 10.1093/jncics/pkad082 -
Urologia Feb 2024The major barriers to phytonutrients in prostate cancer therapy are non-specific mechanisms and bioavailability issues. Studies have pointed to a synergistic combination... (Review)
Review
The major barriers to phytonutrients in prostate cancer therapy are non-specific mechanisms and bioavailability issues. Studies have pointed to a synergistic combination of curcumin (CURC) and ursolic acid (UA). We investigate this combination using a systematic review process to assess the most likely mechanistic pathway and human testing in prostate cancer. We used the PRISMA statement to screen titles, abstracts, and the full texts of relevant articles and performed a descriptive analysis of the literature reviewed for study inclusion and consensus of the manuscript. The most common molecular and cellular pathway from articles reporting on the pathways and effects of CURC ( = 173) in prostate cancer was NF-κB ( = 25, 14.5%). The most common molecular and cellular pathway from articles reporting on the pathways and effects of UA ( = 24) in prostate cancer was caspase 3/caspase 9 ( = 10, 41.6%). The three most common molecular and cellular pathway from articles reporting on the pathways and effects of both CURC and UA ( = 193) in prostate cancer was NF-κB ( = 28, 14.2%), Akt ( = 22, 11.2%), and androgen ( = 19, 9.6%). Therefore, we have identified the potential synergistic target pathways of curcumin and ursolic acid to involve NF-κB, Akt, androgen receptors, and apoptosis pathways. Our review highlights the limited human studies and specific effects in prostate cancer.
Topics: Male; Humans; Ursolic Acid; Curcumin; NF-kappa B; Signal Transduction; Proto-Oncogene Proteins c-akt; Apoptosis; Triterpenes; Prostatic Neoplasms
PubMed: 37776274
DOI: 10.1177/03915603231202304 -
Clinical Breast Cancer Dec 2023Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a... (Meta-Analysis)
Meta-Analysis Review
Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug-conjugate (ADC), primarily used in the treatment of HER2-positive breast cancer. This study aimed to conduct a systematic review to evaluate the efficacy and safety of T-DXd in treating breast cancer, based on clinical trials. A systematic search of the literature was conducted to identify clinical trials investigating the efficacy and safety of T-DXd in breast cancer. Clinical trials of any phase were included. Outcome measures were any adverse events and survival. Meta-analysis was conducted where possible. Pooled prevalence for each adverse event of any grade and grade 3 or greater were estimated. Progression-free survival (PFS), overall survival (OS) and objective response rates (ORRs) were also reported to evaluate the efficacy of T-DXd in breast cancer. A total of 1593 patients from 6 clinical trials were included. Common adverse events of any grade were nausea, anemia, neutropenia, vomiting, fatigue, constipation and diarrhea, occurring in greater than 30% of cases. In terms of adverse events of grade 3 or more, only anemia and neutropenia occurred at a relatively high rate. Median PFS ranged from 11.1 to 22.1 months. There was evidence of a benefit of T-DXd compared to controls in terms of both PFS (OR: 0.38; 95% CI: 0.32, 0.45) and OS (OR: 0.61; 95% CI: 0.48, 0.78). ORRs ranged from 37% to 79.9%. The present systematic review shows evidence that T-DXd is a safe and effective agent in the treatment of breast cancer based on currently available data. The most common adverse events affected the blood, lymphatic and gastrointestinal systems. Interstitial lung disease (ILD) is a notable and potentially serious adverse event.
Topics: Humans; Female; Breast Neoplasms; Trastuzumab; Camptothecin; Neutropenia; Anemia; Receptor, ErbB-2
PubMed: 37775347
DOI: 10.1016/j.clbc.2023.09.005 -
Ecotoxicology and Environmental Safety Oct 2023Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry....
Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry. The critical issue that needs to be solved urgently is to evaluate the safety of traditional Chinese medicine systematically and effectively. Podophyllotoxin (PPT) is a highly active compound extracted from plants of the genus Podophyllum such as Dysosma versipellis (DV). However, its high toxicity and toxicity to multiple target organs affect the clinical application, such as the liver and kidney. Based on the concurrent effects of PPT's medicinal activity and toxicity, it would be a good example to conduct a systematic review of its safety. Therefore, this study revolves around the Toxicological Evidence Chain (TEC) concept. Based on PPT as the main toxic constituent in DV, observe the objective toxicity impairment phenotype of animals. Evaluate the serum biochemical indicators and pathological tissue sections for substantial toxic damage results. Using metabolomics, lipidomics, and network toxicology to evaluate the nephrotoxicity of PPT from multiple perspectives systematically. The results showed that PPT-induced nephrotoxicity manifested as renal tubular damage, mainly affecting metabolic pathways such as glycerophospholipid metabolism and sphingolipid metabolism. PPT inhibits the autophagy process of kidney cells through the PI3K/Akt/mTOR and Nrf2/HO1 pathways and induces the activation of oxidative stress in the body, thereby causing nephrotoxic injury. This study fully verified the feasibility of the TEC concept for the safety and toxicity evaluation of traditional Chinese medicine. Provide a research template for systematically evaluating the safety of traditional Chinese medicine.
Topics: Animals; Rats; Kidney; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; Podophyllotoxin; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases; Podophyllum; Drugs, Chinese Herbal
PubMed: 37651795
DOI: 10.1016/j.ecoenv.2023.115392 -
Journal of Cardiovascular Translational... Apr 2024Activated neutrophils release a range of inflammatory products that represent potential biomarkers, and there is interest in the prognostic value of these in acute... (Meta-Analysis)
Meta-Analysis
Activated neutrophils release a range of inflammatory products that represent potential biomarkers, and there is interest in the prognostic value of these in acute coronary syndrome (ACS) patients. We conducted a systematic review to examine neutrophil-enriched biomarkers and the occurrence of major adverse cardiovascular events (MACE) in patients with ACS. We identified twenty-seven studies including 17,831 patients with ACS. The most studied biomarkers were neutrophil gelatinase-associated lipocalin (NGAL) and myeloperoxidase (MPO). Meta-analyses showed that elevated NGAL was associated with higher MACE rates (unadjusted risk ratio (RR) 1.52, 95% CI 1.12-2.06, p = 0.006) as were elevated MPO levels (unadjusted RR 1.61, 95% CI 1.22-2.13, p = 0.01). There was limited data suggesting that increased levels of calprotectin, proteinase-3 and double-stranded DNA were also associated with MACE. These results suggest that higher levels of neutrophil-enriched biomarkers may be predictive of MACE in patients with ACS, although higher-quality studies are needed to confirm these observations.
Topics: Humans; Acute Coronary Syndrome; Biomarkers; Neutrophils; Prognosis; Lipocalin-2; Peroxidase; Predictive Value of Tests; Time Factors; Risk Assessment; Male; Risk Factors; Female; Up-Regulation; Neutrophil Activation; Middle Aged; Aged
PubMed: 37594719
DOI: 10.1007/s12265-023-10425-2